Glofitamab Plus Chemo Wins European Approval for R/R DLBCL

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The European Commission has approved glofitamab (Columvi) in combination with gemcitabine and oxaliplatin for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified who are ineligible for autologous stem cell transplant (ASCT).1

This decision marks the first approval of a bispecific antibody–based regimen for European patients with R/R DLBCL following initial therapy.

Regulatory approval was supported by results from the phase 3 STARGLO study (NCT04408638), in which glofitamab plus gemcitabine and oxaliplatin demonstrated a 41% reduction in the risk of death compared with rituximab (Rituxan) plus gemcitabine and oxaliplatin at a median follow-up of 11.3 months (95% CI, 9.6-12.7) at the study’s primary analysis (HR, 0.59; 95% CI, 0.40-0.89; P = .011).1,2

At at updated analysis at a median follow-up of 20.7 months, the median overall survival (OS) was 25.5 months (95% CI, 18.3-not evaluable) for glofitamab plus gemcitabine and oxaliplatin compared with 12.9 months (95% CI, 7.9-18.5) for rituximab plus gemcitabine and oxaliplatin (HR, 0.62; 95% CI, 0.43-0.88).2

At the primary analysis and a median follow-up of 11.3 months, findings showed the glofitamab regimen reduced the risk of disease progression or death by 63% compared with the control regimen (HR, 0.37; 95% CI, 0.25-0.55; P < .0001).1 The complete response (CR) rates were 58.5% for the glofitamab arm vs 25.3% for the control arm (difference, 33.2%; 95% CI, 20.9%-45.5%).

The safety profile was consistent with the known effects of the individual agents.

“People with relapsed/refractory DLBCL not eligible for ASCT represent a challenging population, especially those with primary refractory disease or early relapse whose need for a readily accessible and effective therapy is insufficiently addressed globally,” Franck Morschhauser, MD, PhD, professor of hematology at the University Hospital Lille and STARGLO study investigator, stated in a news release. “This new [glofitamab] combination is immediately available if a patient’s cancer returns or doesn’t respond to first-line therapy, which is a welcome addition to manage DLBCL.”

In December 2025, the FDA accepted a supplemental biologics license application (sBLA) seeking the approval of glofitamab-gxbm in combination with gemcitabine and oxaliplatin for the treatment of patients with relapsed/refractory DLBCL who have received at least 1 prior line of therapy and who are not candidates for ASCT.3 The sBLA was also supported by data from STARGLO.

STARGLO Trial Design

The phase 3 STARGLO study was a multicenter, open-label, randomized clinical trial designed to evaluate the efficacy and safety of glofitamab in combination with gemcitabine and oxaliplatin compared with rituximab plus gemcitabine and oxaliplatin in patients at least 18 years of age with relapsed/refractory DLBCL who were ineligible for ASCT and had received 1 or more prior lines of therapy.2

Patients were randomly assigned in a 2:1 fashion to receive glofitamab plus gemcitabine and oxaliplatin or rituximab plus gemcitabine and oxaliplatin. In the experimental arm, glofitamab was administered in a step-up dosing regimen to a target of 30 mg, and it was given for a total of eight cycles in combination with chemotherapy, followed by 4 cycles alone. In the control arm, rituximab was given at 375 mg/m2 for a total of 8 cycles. In both arms, patients received gemcitabine at 1000 mg/m2 and oxaliplatin at 100 mg/m2 for a total of eight cycles.

The primary end point of the study was OS, with secondary end points including progression-free survival, CR rate, objective response rate, duration of response, and safety/tolerability.

Safety Analyses

Across the safety population, all patients (n = 180) treated with the glofitamab-based regimen and 96% of patients in the rituximab-based comparator arm (n = 88) experienced at least 1 adverse effect during the study period. Cytokine release syndrome (CRS) was reported in 76 of 172 patients (44%) exposed to glofitamab; the majority of CRS events were low grade and manageable, consistent with the known safety profile of glofitamab from prior clinical investigations.

Treatment-related mortality was reported in both arms. Five patients (3%) in the glofitamab group experienced deaths deemed related to study treatment, compared with 1 patient (1%) in the rituximab group.

“Glofitamab is the first treatment of its kind to improve survival outcomes for people with DLBCL whose cancer has returned after first-line therapy,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, added in a news release.1 “With this approval, glofitamab can now benefit patients even earlier in their treatment, adding to its existing value as an important treatment for DLBCL.”

References

1. European Commission approves Roche’s Columvi as the first bispecific antibody for diffuse large B-cell lymphoma after initial therapy. April 13, 2025. Accessed April 14, 2025. https://www.roche.com/investors/updates/inv-update-2025-04-14
2. Abramson JS, Ku M, Hertzberg M, et al. Glofitamab plus gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx for relapsed or refractory diffuse large B-cell lymphoma (STARGLO): a global phase 3, randomised, open-label trial. Lancet. 2024;404(10466):1940-1954. doi:10.1016/S0140-6736(24)01774-4
3. FDA accepts supplemental biologics license application for Genentech’s Columvi combination for people with relapsed or refractory diffuse large B-cell lymphoma. News release. Genentech. December 4, 2024. Accessed April 14, 2025. https://www.gene.com/media/press-releases/15045/2024-12-04/fda-accepts-supplemental-biologics-licen